Macrocyclic compounds, e.g., zearalenone-like macrolides such as F152 (LL-Z1640-2), have advantageous biological properties. For example, F152 and certain isomers
thereof inhibit the phosphorylating enzyme Map/Erk kinase (MEK). Moreover, derivatives of F152 also have exhibited activity as tyrosine kinase inhibitors, inhibitors of other protein kinases, e.g., MEK1, inhibitors of NF-κB activation, and inhibitors AP-1 activation, to name a few. Often, however, F152 and derivatives thereof are obtained by fermentation techniques and modifications to the natural product and thus were limited in the number and types of derivatives that could be prepared and evaluated for biological activity.
Chemical synthesis of F152 and derivatives have also been disclosed (see, e.g., WO 03/076424), however, such syntheses are often complex and have many chromatographic purification steps in order to remove impurities.